We have preliminary clinical evidence that the enzyme esterase D may be a genetic marker for the human intraocular neoplasm, retinoblastoma. It is known that a gene for retinoblastoma (Rb) and the gene for esterase D (Es D) are located on chromosome 13. We propose to investigate the suggested linkage between Rb and Es D by examining cultured tumor cells for simultaneous Rb and Es D loci delection. Multiple human retinoblastoma cell lines will be transplanted into the nude (athymic) mouse from various hereditary and sporadic cases of retinoblastoma. These tumors will then be transferred into tissue culture. The linkage of the Rb and Es D loci will be studied by examining the karotype of the tumor lines for deletions in chromosme 13 using banding techniques. Levels of esterase D enzyme activity using a quantitative assay will be correlated with the karotypic findings. Direct preparations from the original tumor specimen and short term primary culture will also be examined for their chromosomal pattern and esterase D activity. Family studies in cases of hereditary retinoblastoma will be investigated concurrently as another way to establish this linkage. If we are able to confirm the presence of a marker for retinoblastoma, this information may also be valuable for improving family counseling and prenatal diagnosis families at risk for developing retinoblastoma.